Wound healing is a dynamic process, which consists of hemostasis, inflammation, proliferation and remodeling. Fibronectin, an extracellular matrix (ECM) glycoprotein, plays important roles in different stages of wound healing, with the main function being cellular adhesion and mediation of cell migration. Fibronectin interacts and activates cell surface integrin receptors, which in turn recruits a series of cellular proteins to connect with the actin cytoskeleton inside the cell, initiating the formation of integrin based adhesive organelles, focal adhesions (FAs). The coupling of actin cytoskeleton and ECM fibronectin via FAs dynamically drives directed cell migration in wound healing. At the beginning, cell protrusions characterized by actin polymerization into dense actin network are extended in the direction of migration followed by attachment of the protrusions to ECM fibronectin that forms nascent adhesions (new-born FAs). Subsequently, nascent adhesions become matured and growing in size via myosin II-mediated contractile forces transduced along the bundled actin filaments. Mature FAs transduce contractile forces from the actin cytoskeleton to the ECM fibronectin, thereby pulling the cell body forward. Finally, FA disassembly accompanied with myosin II-driven contractile forces retracts the trailing edge of the cell from the ECM fibronectin. The ECM fibronectin outside the cell links to the actin cytoskeleton inside the cell via FAs in association with the dynamic control of cell adhesion and directed cell migration in wound healing.
There are two forms of fibronectin: plasma fibronectin and cellular fibronectin. Plasma fibronectin is synthesized by hepatocytes into the blood plasma, while cellular fibronectin is produced by many cell types such as fibroblasts, endothelial cells, myocytes and chondrocytes. In wound healing, it has been reported that plasma fibronectin accumulates remarkably in the wound after wounding in vivo, which is crucial for various functions of platelets, fibroblasts and endothelial cells such as adhesion, migration and aggregation, revealing that plasma fibronectin is likely to serve as a suitable substrate to accelerate wound repair in vivo. Indeed, in animal model, provisional matrix containing plasma fibronectin significantly supports epidermal cell adhesion and migration in the re-epithelialization process, showing the clinical potential of plasma fibronectin in human wound healing and tissue repair.
However, the application of plasma fibronectin to human wound healing has not been validated due to the unreliable and expensive sources of human plasma. The fibronectin from human is not suitable for use in medical products because the fibronectin in a cancer patient has a specific abnormal glycosylation modification, which has the effect of promoting cancer metastasis. Therefore, it will lead to medical risks that use the high purity fibronectin from the blood of unknown health donors to other people. In previous publications, the method includes the recombinant of fibronectin proteins by gene recombination and the purification of fibronectin from human blood is flawed. The inventor has demonstrated that the glycans on fibronectin plays an important role in promoting the progress of wound healing, whereas fibronectin, which is expressed by gene recombination, does not contain glycosylation modification, so its effect is a gap.